Clinical and blood rheologic stability in erythropoietin-treated predialysis patients

We assessed human recombinant erythropoietin (rHuEPO) as treatment for anemia in azotemic patients who did not require dialytic therapy. The study group consisted of 5 azotemic men and 5 women (mean serum creatinine concentration 5.2±3.2 mg/dl) whose mean hematocrit was 27.4 + 3.0%. Of these, 5 subjects had diabetic nephropathy. The study was a 12-month rHuEPO maintenance (open label) trial in which a previously established median i.v. dose of 50 U/kg was given three times each week. The rHuEPO was temporarily discontinued when the target hematocrit of 37% was achieved, and after the hematocrit decreased below 35%. it was restarted at half the initial dose. Of the 10 subjects who started the trial. 2 (both nondiabetic) deteriorated early in the study, and before a hematocrit rise was attained commenced maintenance hemodialysis. All subjects completed the year of study and achieved the target hematocrit. Mean hematocrit rose 42% (p <0.001) in a mean period of 3.3± 1.3 months. When treatment was interrupted at a hematocrit of 37%. mean absolute reticulocyte count fell from 1.21 ±0.59% to0.38±0.14% within one week. After rHuEPO was withdrawn, the increase in hematocrit persisted for a mean of 13.0±6.0 days and patients were able to sustain hematocrits above 35% fora mean of 1.44 ±0.6 months. Coincidentally with the rise in hematocrit during rHuEPO treatment, whole-blood viscosity increased significantly (p <0.001) but remained within the range for individuals with normal renal function at an equivalent hematocrit (p≥0.5). Renal function was stable during the year of treatment; the 5 azotemic diabetic subjects began at a mean serum creatinine of 3.5 ±0.28 mg/dl. and ended at a mean of 3.7±0.11 mg/dl. There were no adverse events. We conclude that rHuEPO given intravenously is safe and effective treatment for the anemia of renal insufficiency in patients who do not yet require dialytic therapy.